Evidence map›Paper›PMID 16822849›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2006

Breaking the one antibody-one target axiom.

Fang Guo, Sanjib Das, Barbara M Mueller, Carlos F Barbas, Richard A Lerner, Subhash C Sinha

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed, 1 pooled it
3.9field-weighted citation impact, top 7% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 1 synthesis or guideline pooled it, 31 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Chemically programmed antibodies.Trends in biotechnology · 2014
    Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
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  13. Article
  14. Article
  15. Article
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  17. Article
  18. Targeted instant immunity.Nature biotechnology · 2009
    Article
  19. Instant immunity through chemically programmable vaccination and covalent self-assembly.Proceedings of the National Academy of Sciences of the United States of America · 2009
    Article
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Fang GuoThe Skaggs Institute for Chemical Biology and Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Sanjib Das
Barbara M Mueller
Carlos F Barbas
Richard A Lerner
Subhash C Sinha
Scripps Research Institute · USInstitute for Molecular Medicine · US

Funding

Chemically Programmed Antibodies for Cancer TherapyR01CA104045 · NCI · SCRIPPS RESEARCH INSTITUTE, THE · PI BARBAS, CARLOS F · 2004 to 2010
$2.1M
NCI NIH HHS 5R01 CA104045NCI NIH HHS R01 CA104045
6 · The paper itself

Abstract

Studies at the interface of chemistry and biology have allowed us to develop an immunotherapeutic approach called chemically programmed antibodies (cpAbs), which combines the merits of traditional small-molecule drug design with immunotherapy. In this approach, a catalytic antibody catalyzes the covalent conjugation of a small molecule or peptide to the active site of the antibody, effectively recruiting the binding specificity of the conjugated molecule to the antibody. In essence, this technology provides the tools for breaking the "one antibody-one target axiom" of immunochemistry. Our studies in this area have focused on using the chemistry of the well studied aldolase catalytic antibodies of which mAb 38C2 is a member. Previously, we explored reversible assembly of cpAbs available through diketone chemistry. In this article, we explore a unique proadapter assembly strategy wherein an antibody 38C2-catalyzed transformation unveils a reactive tag that then reacts to form a stable covalent bond with the antibody. An integrin alpha(v)beta 3 antagonist was synthesized with the designed proadapter and studied using human breast cancer cell lines MDA-MB-231 and MDA-MB-435. We demonstrate that this approach allows for (i) the effective assembly of cpAbs in vitro and in vivo, (ii) selective retargeting of 38C2 to integrin alpha(v)beta 3 expressing breast cancer cell lines, (iii) intracellular delivery of cpAbs into cells, (iv) dramatically increased circulatory half-life, and (v) substantial enhancement of the therapeutic effect over the peptidomimetic itself in animal models of breast cancer metastasis. We believe that this technology possesses potential for the treatment and diagnosis of disease.

Indexed as

AnimalsAntibodiesAntigensBreast NeoplasmsCell Line, TumorFemaleHumansImmunologic TechniquesIntegrin alphaVbeta3Lung NeoplasmsMiceMice, SCIDMolecular StructureAntibodiesAntigensIntegrin alphaVbeta3

Identifiers

PMID16822849
PMCPMC1488731
OpenAlexW2076207455

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.